A Novel Bionic Catalyst-Mediated Drug Delivery System for Enhanced Sonodynamic Therapy.
TL;DR: In this article, the authors describe the development of an innovative, multi-use, catalyst-based and improved sonodynamic therapy targeting cancer, through the employment of a sonosensitizing curcumin load embedded within a MnO2 core, together with an extraneous tumor cell membrane component.
Abstract: Ultrasound (US)-triggered sonodynamic therapy (SDT) proves itself to be a formidable tool in the fight against cancer, due to its large spectrum of uses as a non-invasive therapeutic measure, while also demonstrating itself to be a certain improvement upon traditional SDT therapeutics. However, tumor hypoxia remains to be a major challenge for oxygen-dependent SDT. This study describes the development of an innovative, multi-use, catalyst-based and improved SDT targeting cancer, through the employment of a sonosensitizing curcumin (Cur) load embedded within a MnO2 core, together with an extraneous tumor cell membrane component. The latter allows for efficient tumor recognition properties. Hollowed-out MnO2 allows for efficient drug delivery, together with catalyzing oxygen generation from hydrogen peroxide present in tumor tissue, leading to enhanced SDT efficacy through the induction of a reduced hypoxic state within the tumor. In addition, Cur acts as a cytotoxic agent in its own right. The results deriving from in vivo studies revealed that such a biomimetic approach for drug-delivery actually led to a reduced hypoxic state within tumor tissue and a raised tumor-inhibitory effect within mouse models. Such a therapeutic measure attained a synergic SDT-based tumor sensitization treatment option, together with the potential use of such catalysis-based therapeutic formulations in other medical conditions having hypoxic states.
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TL;DR: An intelligent biodegradable hollow manganese dioxide (H-MnO2) nano-platform is developed for not only tumor microenvironment (TME)-specific imaging and on-demand drug release, but also modulation of hypoxic TME to enhance cancer therapy, resulting in comprehensive effects favoring anti-tumor immune responses.
Abstract: Herein, an intelligent biodegradable hollow manganese dioxide (H-MnO2) nano-platform is developed for not only tumor microenvironment (TME)-specific imaging and on-demand drug release, but also modulation of hypoxic TME to enhance cancer therapy, resulting in comprehensive effects favoring anti-tumor immune responses. With hollow structures, H-MnO2 nanoshells post modification with polyethylene glycol (PEG) could be co-loaded with a photodynamic agent chlorine e6 (Ce6), and a chemotherapy drug doxorubicin (DOX). The obtained H-MnO2-PEG/C&D would be dissociated under reduced pH within TME to release loaded therapeutic molecules, and in the meantime induce decomposition of tumor endogenous H2O2 to relieve tumor hypoxia. As a result, a remarkable in vivo synergistic therapeutic effect is achieved through the combined chemo-photodynamic therapy, which simultaneously triggers a series of anti-tumor immune responses. Its further combination with checkpoint-blockade therapy would lead to inhibition of tumors at distant sites, promising for tumor metastasis treatment. MnO2 nanostructures are promising TME-responsive theranostic agents in cancer. Here, the authors develop a nano-platform based on hollow H-MnO2 nanoshells able to modulate the tissue microenvironment, release a drug and inhibit tumor growth alone or in combination with check-point blockade therapy.
1,007 citations
TL;DR: A cancer targeted cascade bioreactor was constructed by embedding glucose oxidase and catalase in the cancer cell membrane-camouflaged porphyrin metal-organic framework of PCN-224 to enhance its cancer targeting and retention abilities and displayed amplified synergistic therapeutic effects of long-term cancer starvation therapy and robust PDT.
Abstract: Selectively cuting off the nutrient supply and the metabolism pathways of cancer cells would be a promising approach to improve the efficiency of cancer treatment. Here, a cancer targeted cascade bioreactor (designated as mCGP) was constructed for synergistic starvation and photodynamic therapy (PDT) by embedding glucose oxidase (GOx) and catalase in the cancer cell membrane-camouflaged porphyrin metal–organic framework (MOF) of PCN-224 (PCN stands for porous coordination network). Due to biomimetic surface functionalization, the immune escape and homotypic targeting behaviors of mCGP would dramatically enhance its cancer targeting and retention abilities. Once internalized by cancer cells, mCGP was found to promote microenvironmental oxygenation by catalyzing the endogenous hydrogen peroxide (H2O2) to produce oxygen (O2), which would subsequently accelerate the decomposition of intracellular glucose and enhance the production of cytotoxic singlet oxygen (1O2) under light irradiation. Consequently, mCGP d...
593 citations
TL;DR: Dr. W. Bu Jiangsu Collaborative Innovation Center for Advanced Inorganic Functional Composites Nanjing Tech University Nanjing 210009 and Prof. J. Shi State Key Laboratory of High Performance Ceramics and Superfi ne Microstructures Shanghai Institute of Ceramic Chinese Academy of Sciences Shanghai 200050.
Abstract: Dr. W. Fan, Prof. W. Bu, Dr. Q. He, Dr. Z. Cui, Dr. Y. Liu, Prof. J. Shi State Key Laboratory of High Performance Ceramics and Superfi ne Microstructures Shanghai Institute of Ceramics Chinese Academy of Sciences Shanghai 200050 , P. R. China E-mail: wbbu@mail.sic.ac.cn; jlshi@mail.sic.ac.cn Prof. W. Bu Jiangsu Collaborative Innovation Center for Advanced Inorganic Functional Composites Nanjing Tech University Nanjing 210009 , P. R. China Dr. B. Shen Institute of Radiation Medicine Fudan University Shanghai 200032 , P. R. China Dr. X. Zheng Department of Radiation Oncology Shanghai Huadong Hospital Fudan University Shanghai 200040 , P. R. China Dr. K. Zhao Department of Radiology Shanghai Cancer Hospital Fudan University Shanghai 200032 , P. R. China
575 citations
TL;DR: A novel dual-activatable fluorescence/MRI bimodal platform is designed for tumor cell imaging by using a redoxable manganese dioxide (MnO2) nanosheet-aptamer nanoprobe, which acts as a DNA nanocarrier, fluorescence quencher, and intracellular glutathione (GSH)-activated MRI contrast agent.
Abstract: A novel dual-activatable fluorescence/MRI bimodal platform is designed for tumor cell imaging by using a redoxable manganese dioxide (MnO2) nanosheet–aptamer nanoprobe. The redoxable MnO2 nanosheet acts as a DNA nanocarrier, fluorescence quencher, and intracellular glutathione (GSH)-activated MRI contrast agent. In the absence of target cells, neither fluorescence signaling nor MRI contrast of the nanoprobe is activated. In the presence of target cells, the binding of aptamers to their targets weakens the adsorption of aptamers on the MnO2 nanosheets, causing partial fluorescence recovery, illuminating the target cells, and also facilitating the endocytosis of nanoprobes into target cells. After endocytosis, the reduction of MnO2 nanosheets by GSH further activates the fluorescence signals and generates large amounts of Mn2+ ions suitable for MRI. This platform should facilitate the development of various dual-activatable fluorescence/MRI bimodalities for use in cells or in vivo.
459 citations
TL;DR: N nanoparticles that release camptothecin in a reactive oxygen species dependent manner, leading to cancer cell death, are used, which overcomes the short lifespan and action range of ROS, avoids the penetration limitation of exogenous light in photodynamic therapy, and is promising for theranostics.
Abstract: Cancer cells exhibit slightly elevated levels of reactive oxygen species (ROS) compared with normal cells, and approximately 90% of intracellular ROS is produced in mitochondria. In situ mitochondrial ROS amplification is a promising strategy to enhance cancer therapy. Here we report cancer cell and mitochondria dual-targeting polyprodrug nanoreactors (DT-PNs) covalently tethered with a high content of repeating camptothecin (CPT) units, which release initial free CPT in the presence of endogenous mitochondrial ROS (mtROS). The in situ released CPT acts as a cellular respiration inhibitor, inducing mtROS upregulation, thus achieving subsequent self-circulation of CPT release and mtROS burst. This mtROS amplification endows long-term high oxidative stress to induce cancer cell apoptosis. This current strategy of endogenously activated mtROS amplification for enhanced chemodynamic therapy overcomes the short lifespan and action range of ROS, avoids the penetration limitation of exogenous light in photodynamic therapy, and is promising for theranostics.
265 citations